Effects of methotrexate on human bone cell responses to mechanical stimulation

Rheumatology
K J ElliotD M Salter

Abstract

Methotrexate (MTX), which is prescribed in the treatment of malignancy and autoimmune disease, has detrimental effects on a number of organ systems, including bone. At present, the exact mechanism of action of MTX on bone at the cellular level is unclear. Mechanical stimuli imparted by stretch, pressure, fluid flow and shear stress result in a variety of biochemical responses that are important in bone metabolism. Cyclical mechanical stimulation at 0.33 Hz induces rapid cell membrane hyperpolarization of human bone cells (HBC) via an integrin-mediated pathway which includes an IL-1beta autocrine/paracrine loop. This study was undertaken to investigate the effect of MTX on responses of HBC to 0.33 Hz mechanical stimulation. Electrophysiological responses of HBC were measured before and after mechanical stimulation at 0.33 Hz in the presence or absence of MTX. Semiquantitative RT-PCR was used to investigate effects of MTX on relative levels of type-1 collagen and bone morphogenetic protein-4 (BMP-4) following 0.33 Hz mechanical stimulation. MTX dose-dependently inhibited HBC hyperpolarization in response to 0.33 Hz mechanical stimulation. Production/release of IL-1beta was inhibited by MTX, whereas its effects on target cells wer...Continue Reading

Citations

Sep 11, 2007·Surgical Neurology·Arnaldo Neves Da SilvaDavid Schiff
Nov 1, 2020·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·F RobinP Guggenbuhl
Jul 3, 2021·International Journal of Molecular Sciences·Xia XuLifang Hu

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